Dimethylformamide → 6-[(4-{3-cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}piperazin-1-yl)carbonyl]-5-fluoronicotinonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-{4-[(5-chloro-3-fluoropyridin-2-yl)carbonyl]piperazin-1-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (15 mg, 0.030 mmol, from Example 1), 2-(Dicyclohexylphosphino)-2′,6′-dimethoxy-1,1′-biphenyl (3.7 mg, 0.0091 mmol), Tris(dibenzylideneacetone)dipalladium(0) (3.3 mg, 0.0036 mmol) and zinc cyanide (18 mg, 0.15 mmol) in DMF (0.50 mL, 6.4 mmol) and one drop of water was degassed by purging with a stream of nitrogen for 5 minutes, then was heated in the microwave for 15 minutes at 150° C. Preparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH, was used to purify the product (6 mg, 40%). 1H NMR (300 MHz, d6-dmso): δ 12.10 (br s, 1H), 8.93 (t, 1H), 8.81 (s, 1H), 8.68 (s, 1H), 8.59 (dd, 1H), 8.37 (s, 1H), 7.60 (d, 1H), 6.97 (d, 1H), 4.98 (tt, 1H), 3.65-3.58 (m, 2H), 3.25-3.19 (m, 2H), 3.19-3.13 (m, 2H), 2.92-2.78 (m, 2H), 2.66-2.25 (m, 4H); LCMS (M+H)+: 485.2.

Provenance & Evidence